Mr. Sittig, who led the creation of the now ubiquitous “like” button and introduced friend photo tags, is leaving just two years after rejoining the company as “design strategy lead.” According to one person with knowledge of the matter, Mr. Sittig had become deeply involved in Facebook’s mobile projects over the past year.

Mr. Sittig was one of the earliest employees at Facebook, recruited in 2005 by Sean Parker, the former Facebook president, to help with the fledgling site’s design. Mr. Sittig briefly left the company in 2010, at a time when many early Facebook employees were leaving to build new startups or pursue other opportunities. He returned in February 2011.

In a sign of how close Messrs. Sittig and Zuckerberg have been, the Facebook CEO attended Mr. Sittig’s 2011 wedding.

His departure comes as Facebook ramps up its efforts on mobile. Despite its size, the company’s plans to dominate smartphones is threatened by younger startups, such as Whatsapp, and larger rivals, including Apple and Google, which have the advantage of owning their own operating systems.

Shares of Facebook rose more than 5% to close at $30.59, rising above $30 for the first time in roughly six months.